Adverse cutaneous photosensitivity reactions following exposure to environmental chemicals and light have been reported with increasing frequency during recent years. The broad objective of our research is to define more precisely the underlying mechanisms of these adverse photoresponses. Our approach is to work in the interface between isolated tube photochemical studies and the physiologic, but highly complex photobiologic responses in the whole organism. Specifically, we propose to detect and quantitate, in an in vivo mammalian model, the precise cellular and subcellular localization of exogenous photosensitizers such as chlorpromazine, anthracene and psoralen, as well as endogenous ones such as porphyrins. In addition, the initial photochemical reactions between environmental chemicals and biologic macromolecules initiating photosensitivity responses will be investigated. The effects of metabolic pathways on the activity of photosensitizers will also be assayed. A newly developed fluorescence microscope will be employed to localize the photosensitizers and define their intracellular environment by fluorescence polarization, emission spectra and excited state lifetime measurements. These in situ studies will complement structural and mechanistic studies in the interaction of photosensitizers with proteins, nucleic acids and membrane lipids in model systems. Results will be directed toward developing agents that will protect against or repair photodamage. Finally, we will continue clinical studies in man concerned with early recognition of adverse photosensitivity reactions due to agents introduced into our environment by new developments in industry, manufacturing and medical practices.